Ebook Embryology at a glance: Part 1

Embryology
at a Glance


Companion website
This book is accompanied by a website containing a link to Dr Webster’s website and podcasts:
www.wiley.com/go/embryology


Embryology
at a Glance
Samuel Webster
Lecturer in Anatomy & Embryology
College of Medicine
Swansea University
Swansea, UK

Rhiannon de Wreede
Honorary Lecturer
College of Medicine
Swansea University
Swansea, UK

A John Wiley & Sons, Ltd., Publication


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Library of Congress Cataloging-in-Publication Data
Webster, Samuel, 1974  Embryology at a glance / Samuel Webster, Rhiannon de Wreede.
    p. ; cm. – (At a glance series)
  Includes bibliographical references and index.
  ISBN 978-0-470-65453-8 (pbk. : alk. paper)
  I.  De Wreede, Rhiannon.  II.  Title.  III.  Series: At a glance series (Oxford, England).

  [DNLM: 1. Embryonic Development. QS 604]
  612.6'4–dc23

2011049102
A catalogue record for this book is available from the British Library.
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Set in 9/11.5pt Times by Toppan Best-set Premedia Limited
1  2012


Contents
Preface  6
Acknowledgements  7
List of abbreviations  8
Timeline  9
Part 1  Early development 
  1  Embryology in medicine  10
  2  Language of embryology  12
  3  Introduction to development  14
  4  Embyonic and foetal periods  16
  5  Mitosis  18
  6  Meiosis  20
  7  Spermatogenesis  22
  8  Oogenesis  24
  9  Fertilisation  26
10  From zygote to blastocyst  28
11  Implantation  30

12  Placenta  32
13  Gastrulation  34
14  Germ layers  36
15  Neurulation  38
16  Neural crest cells  40
17  Body cavities (embryonic)  42
18  Folding of the embryo  44
19  Segmentation  46
20  Somites  48
Part 2  Systems development 
21  Skeletal system (ossification)  50
22  Skeletal system  52
23  Muscular system  54

24  Musculoskeletal system: limbs  56
25  Circulatory system: heart tube  58
26  Circulatory system: heart chambers  60
27  Circulatory system: blood vessels  62
28  Circulatory system: embryonic veins  64
29  Circulatory system: changes at birth  66
30  Respiratory system  68
31  Digestive system: gastrointestinal tract  70
32  Digestive system: associated organs  72
33  Digestive system: congenital anomalies  74
34  Urinary system  76
35  Reproductive system: ducts and genitalia  78
36  Reproductive system: gonads  80
37  Endocrine system  82
38  Head and neck: arch I  84
39  Head and neck: arch II  86

40  Head and neck: arch III  88
41  Head and neck: arches IV–VI  90
42  Central nervous system  92
43  Peripheral nervous system  94
44  The ear  96
45  The eye  98
Part 3  Self-assessment 
MCQs  101
MCQ answers  106
EMQs  107
EMQ answers  108
Glossary  109
Index  114

Companion website
This book is accompanied by a website containing a link to Dr Webster’s website and podcasts:
www.wiley.com/go/embryology

Contents  5


Preface
We wrote this book for our students; those studying medicine with
us, those listening to the podcasts wherever they may be, and those
studying the other forms that biology takes on their paths to
whatever goals they may have in life. We have introduced many
students to the fascinating and often surprising processes of
embryological development, and we hope to do the same in this
book. It is written for anyone wondering, “where did I come
from?”

The content of this book extends beyond the curricula of most
medicine, health and bioscience teaching programmes in terms of
breadth, but we have limited its depth. Many embryology text-

6  Preface

books cover development in detail, but students struggle to get
started, and to get to grips with early concepts. Hopefully we have
addressed these difficulties with this book.
We hope that you will use this book to begin your studies of
embryology and development, but also that you will return to it
when preparing for assessments or checking your understanding.
You will find example assessment questions in Chapters 46 and
47, and a glossary in Chapter 48.
Let this be the start of your integration of embryonic development with anatomy, to the ends of improved understanding and
better patient care or scientific insight.


Acknowledgements
Thank you to Kim and Robin for being so encouraging and
putting up with the time demands of completing this book. We
would also like to thank the editors at Wiley-Blackwell for leading
us through this process and for their support and encouragement,
and Jane Fallows for all her work with the illustrations.

Acknowledgements  7


List of abbreviations
AER

CAM
CN
CSF
ECMO
FGF
FSH
GnRH
HbF
hCG
hCS
IUD
IUGR

Apical ectodermal ridge
Cell adhesion molecule
Cranial nerve
Cerebrospinal fluid
Extracorporeal membrane oxygenation
Fibroblast growth factor
Follicle stimulating hormone
Gonadotrophin releasing hormone
Foetal haemoglobin
Human chorionic gonadotrophin
Human chorionic somatomammotrophin
Intrauterine device – contraceptive device
Intrauterine growth restriction

8  List of abbreviations

IVC

IVD
IVF
LH
LMP
PDA
PFO
PTH
PZ
Rh
SVC
TGF
ZPA

Inferior vena cava
Intervertebral disc
In vitro fertilisation
Luteinising hormone
Last menstrual period
Patent ductus arteriosus
Patent foramen ovale
Parathyroid hormone
Proliferating zone
Rhesus
Superior vena cava
Transforming growth factor
Zone of polarising activity


Timeline

0

10

Days
30

20

40

50

60

10

20

Weeks

30

40

Adult
Death
Puberty Menopause

Language of embryology (Chapter 2)

Introduction to development (Chapter 3)
Embryonic and foetal periods (Chapter 4)
Spermatogenesis (Chapter 7)
Oogenesis (Chapter 8)
Fertilisation (Chapter 9)
From zygote to blastocyst (Chapter 10)
Implantation (Chapter 11)
Placenta (Chapter 12)
Gastrulation (Chapter 13)
Formation of germ layers (Chapter 14)
Formation of the heart tube (Chapter 25)
Folding of the embryo (Chapter 18)
Neurulation (Chapter 15)
Segmentation (Chapter 19)
Formation of blood vessels (Chapter 27)
Somite development (Chapter 20)
Development of digestive system (Chapter 31)
Development of body cavities (Chapter 17)
Development of urinary system (Chapter 34)
Development of head and neck structures (Chapter 38–41)
Development of the eye (Chapter 45)
Migration of neural crest cells (Chapter 16)
Development of muscular system (Chapter 23)
Development of the ear (Chapter 44)
Development of central nervous system (Chapter 42)
Cranial neuropore closes (Chapter 15)
Development of endocrine system (Chapter 36)
Caudal neuropore closes (Chapter 15)
Heart tube divides into four chambers (Chapter 26)
Development of skeletal system (Chapter 22)

Development of peripheral nervous system (Chapter 43)
Development of musculoskeletal system (Chapter 24)
Development of respiratory system (Chapter 30)
Formation of the atrial septa (Chapter 26)
Ossification of skeletal system (Chapter 21)
Development of reproductive system (Chapter 35)
Foetus can hear external sounds (Chapter 44)
0

10

20

30
Days

40

50

60

10

20

Weeks

30

40

Puberty Menopause
Adult
Death

Time line  9


1

Embryology in medicine

Figure 1.1
The early embryo develops from a simple group of cells into complex shapes and structures in the early weeks

Figure 1.2
Development continues beyond embryology and
the foetus continues to grow and mature
Figure 1.3
Development of biological structures and
systems continues through childhood,
adolescence and into adulthood. Changes
continue to occur throughout life

Embryology at a Glance, First Edition. Samuel Webster and Rhiannon de Wreede.

10  © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

What is embryology?
Animals begin life as a single cell. That cell must produce new cells
and form increasingly complex structures in an organised and
controlled manner to reliably and successfully build a new organism (Figures 1.1 and 1.2). As an adult human may be made up
of around 100 trillion cells this must be an impressively wellchoreographed compendium of processes.
Embryology is the branch of biology that studies the early formation and development of these organisms. Embryology begins
with fertilisation, and we have included the processes that lead to
fertilisation in this text. The human embryonic period is completed
by week 8, but we follow development of many systems through
the foetal stages, birth and, in some cases, describe how changes
continue to occur into infancy, adolescence and adult life
(Figure 1.3).

Aims and format
This book aims to be concise but readable. We have provided a
page of text accompanied by a page of illustrations in each chapter.
Be aware that the concise manner of the text means that the topic
is not necessarily comprehensive. We aim to be clear in our descriptions and explanations but this book should prepare you to move
on to more comprehensive and detailed texts and sources.

Why study embryology?
Our biological development is a fascinating subject deserving
study for interest’s sake alone. An understanding of embryological
development also helps us answer questions about our adult
anatomy, why congenital abnormalities sometimes occur and gives
us insights into where we come from. In medicine the importance
of an understanding of normal development quickly becomes clear
as a student begins to make the same links between embryology,
anatomy, physiology and neonatal medicine.
The study of embryology has been documented as far back as

the sixth century bc when the chicken egg was noted as a perfect
way of studying development. Aristotle (384–322 bc) compared
preformationism and epigenetic theories of development. Do
animals begin in a preformed way, merely becoming larger, or do
they form from something much simpler, developing the structures
and systems of the adult in time? From studies of chickens’ eggs
of different days of incubation and comparisons with the embryos
of other animals Aristotle favoured epigenetic theory, noting
similarities between the embryos of humans and other animals in
very early stages. In a chicken’s egg, a beating heart can be
observed with the naked eye before much else of the chicken has
formed.

Aristotle’s views directed the field of embryology until the invention of the light microscope in the late 1500s. From then onwards
embryology as a field of study was developed.
A common problem that students face when studying embryology is the apparent complexity of the topic. Cells change names,
the vocabulary seems vast, shapes form, are named and renamed,
and not only are there structures to be concerned with but also the
changes to those structures with time. In anatomy, structures
acquire new names as they move to a new place or pass another
structure (e.g. the external iliac artery passes deep to the inguinal
ligament and becomes the femoral artery). In embryology, cells
acquire new names when they differentiate to become more specialised or group together in a new place; structures have new
names when they move, change shape or new structures form
around them. With time and study students discover these processes, just as they discover anatomical structures.

Embryology in modern medicine
If a student can build a good understanding of embryological and
foetal development they will have a foundation for a better understanding of anatomy, physiology and developmental anomalies.
For a medical student it is not difficult to see why these subjects

are essential. If a baby is born with ‘a hole in the heart’, what does
this mean? Is there just one kind of hole? Or more than one? Where
is the hole? What are the physiological implications? How would
you repair this? If that part of the heart did not form properly
what else might have not formed properly? How can you explain
to the parents why this happened, and what the implications are
for the baby and future children? A knowledge of the timings at
which organs and structures develop is also important in determining periods of susceptibility for the developing embryo to environmental factors and teratogens.

Why read this book?
We appreciate that the subject of embryology still induces concern
and despair in students. However, if it helps you in your profession
you should want to dig deep into the wealth of understanding it
can give you. We also appreciate that you have enough to learn
already and so this book hopes to represent embryology in an
accessible format, as our podcasts try to do.
One thing that has not changed with the development of embryology as a subject is that the more information that is gathered,
the more numerous are the questions left unanswered. For example,
we barely mention the molecular aspects of development here.
Should your interest in embryology and mechanisms of development be aroused by this book, we hope that you will seek out more
detailed sources of information to consolidate your learning.

Embryology in medicine  Early development  11


2

Language of embryology
Superior

Median (sagittal) plane

Medial

Anterior
(ventral)

Lateral

Posterior
(dorsal)

Rostral
Ventral

Dorsal
Caudal

Proximal

Distal
Inferior
Figure 2.1
The anatomical position
The adult anatomical position can be used to describe
structures that are medial or lateral relative to the
median sagittal plane, and proximal or distal in the limbs.
These also apply to the embryo

Coronal plane

Figure 2.4
The coronal plane in the embryo
and the adult refer to a plane
of section cut like this

Figure 2.2
The surfaces of the embryo that rostral,
caudal, dorsal and ventral refer to

Figure 2.3
Note how the descriptions of superior, inferior,
anterior and posterior of the adult anatomical
position relate to the descriptions of the embryo

Transverse
planes

Figure 2.5
Transverse planes are cut across
the embryo as in this diagram,
perpendicular to the coronal plane

Embryology at a Glance, First Edition. Samuel Webster and Rhiannon de Wreede.

12  © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

Figure 2.6
Oblique planes are cut in directions unlike the
other planes. They do not cut along a clear X,

Y or Z axis


Time period: day 0–266
Introduction
The language used to describe the embryo and the developmental
processes that mould it is necessarily descriptive. It is similar to
anatomical terminology, but there are some common differences
that the reader should be aware of.
The embryo does not, and for most of its existence cannot, take
on the anatomical position. The embryo is more curved and folded
than the erect adult. The adult anatomical position is described as
the body being erect with the arms at the sides, palms forward and
thumbs away from the body (Figure 2.1). The anatomical relationships of structures are described as if in this position, so for the
embryo we need to rethink this a little.

Cranial–caudal
Anatomically speaking, you may interchangeably use cranial or
superior, and caudal or inferior. Cranial clearly refers to the head
end of the embryo and caudal (from the Latin word cauda, meaning
‘tail’) refers to the tail end (Figure 2.2). If you imagine the early
sheet of the embryo with the primitive streak (see Chapter 13)
showing us the cranial and caudal ends, you can imagine that it
can be clearer to use these terms rather than superior and
inferior.
The term ‘rostral’ may also be used in place of cranial. Rostral
is derived from the Latin word rostrum, meaning ‘beak’.

Dorsal–ventral
The dorsal surface of the embryo and the adult is the back (Figure

2.2). Dorsal also refers to the surface of the foot opposite to the
plantar surface, the surface of the tongue covered with papillae,
and the superior surface of the brain, so some care is needed.
The ventral surface of the embryo is the front or anterior of the
embryo, opposite the dorsal surface.

Medial–lateral
As with adult anatomy, structures nearer to the midline sagittal
plane are more medial, and structures further from the midline are
more lateral (Figure 2.3). This also helps us describe the left–right
axis of the embryo.

Proximal–distal
Proximal and distal are a little different from medial and lateral,
but similarly describe structures near to the centre of the body
(proximal) and further from the centre (distal) (Figure 2.1). These
terms are typically used to describe limb structures. The hand is
distal to the elbow, for example.

Sections
Often, to show the parts of the embryo being described, illustrations must be of a section of the embryo or a structure. These
sections may be transverse, median, coronal or oblique. You can
see these planes of sections in the illustrations on the opposite page
(Figures 2.4–2.6).

Language of embryology  Early development  13


3

Introduction to development

Proliferation

Hypertrophy

Accretion
Anterior

Limb bud

Humerus
Carpals

Morphogen
gradient

Figure 3.1
Mechanisms of growth

Figure 3.2
Morphogen secretion organises
cells during avian limb bud
development

Posterior

Grafted cells

Chronic cavity

Ulna
Radius

Grafted cells

Normal polarising
region

Extra embryonic
mesoderm
Epiblast
Hypoblast

Normal polarising
region

Normal polarising
region

Amniotic cavity
Connecting stalk
Foregut
Midgut

Secondary
yolk sac

Hindgut

Cytotrophoblast

Figure 3.3
An example of morphogenesis
The simple sheet of epiblast forms 3 layers that change shape to become the tube of the gut and give the general shape of the embryo

Time period: day 0 to adult

knowledge we become able to understand how these processes can
be interfered with, and how abnormalities arise.

Development
Development, in this book, describes our journey from a single cell
to a complex multicellular organism. Development does not end
at birth, but continues with childhood and puberty to early
adulthood.
We must describe how a cell from the father and a cell from the
mother combine to form a new genetic individual, and how this
new cell forms others, how they become organised to form new
shapes, specialised interlinked structures, and grow. With this

Growth
Growth may be described as the process of increasing in physical
size, or as development from a lower or simpler form to a higher
or more complex form.
In embryology, growth with respect to a change in size may
occur through an increase in cell number, an increase in cell size
or an increase in extracellular material (Figure 3.1).

Embryology at a Glance, First Edition. Samuel Webster and Rhiannon de Wreede.

14  © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.


Increasing cell number occurs by cells dividing to produce
daughter cells by proliferation. Proliferation is a core mechanism
of increasing the size of a tissue or organism, and is also found in
adult tissues in repair or where there is an expected continual loss
of cells such as in the skin or gastrointestinal tract. Stem cells are
particularly good at proliferating.
An increase in cell size occurs by hypertrophy. In adults, muscle
cells respond to weight training by hypertrophy, and this is one
way in which muscles become larger. During development, hypertrophy of cartilage cells during endochondral ossification is an
important part of the growth of long bones. Be aware that the term
hypertrophy can also be used to describe a structure that is larger
than normal.
Cells may surround themselves with an extracellular matrix,
particularly in connective tissues such as bone and cartilage. By
accretion these cells increase the size of the tissue by increasing the
amount of extracellular matrix, either as part of development or
in response to mechanical loading.
Cells may also die by programmed cell death, or apoptosis. This
might be considered an opposite to growth, and in development is
an important method of forming certain structures like the fingers
and toes.

Differentiation
During development, cells become specialised as they move from
a multipotent stem cell type towards a cell type with a particular
task, such as a muscle cell, a bone cell, a neuron or an epithelial

cell. When the cell becomes more specialised it is considered to
have differentiated into a mature cell type. If that cell divides, its
daughter cells will also be of that mature cell type.
In humans, a mature cell is unlikely to dedifferentiate back into
a stem cell, but the process by which this can occur is being
exploited in the laboratory with the aim of producing stem cells
from adult tissues. These stem cells could then be pushed to differentiate into the cell type needed to grow new tissue or treat a
disease.

Signalling
A signal from one group of cells influences the development of
another (adjacent, nearby or distant) group of cells. Hormones act
as signals, for example. For a cell to be affected by a signal it must
possess an appropriate receptor.
In the embryo the signalling of a vast array of different proteins
by different groups of cells allows those cells to gain information
about their current and future tasks, be that migration, proliferation, differentiation or something else.

Organisation
Early in development the ball of cells or simple sheets of the
embryo do not give much clue about which cells will form which
structures. It is difficult to determine which part will become the
head and which will become the tail. However, the cells are aware

of their position and the roles that they will have and we can
see this by looking at the signalling proteins and connections
between cells.
For example, the upper limb begins to develop as a simple bud
of cells. The cells in that bud must be organised to produce the
structures of the arm, the forearm and the hand. The ulna bone

must form in the right place relative to the radius, and the thumb
must form appropriately in relation to the fingers. This may occur
partly because a group of cells on the caudal aspect of the limb
bud produces a morphogen that diffuses across the early limb bud
(Figure 3.2). Cells near the site of morphogen production experience a high concentration, and cells further away on the cranial
side of the bud experience a lower concentration. Development of
these cells progresses differently as a result. If experimentally you
transplant some of the morphogen-producing cells to the cranial
part of the limb bud, duplicate digital structures form. See Chapter
23 for more about limb development.
This is one example of how cells organise themselves and others
during development. With organisation, structure follows.

Morphogenesis
The formation of shape during development is morphogenesis.
Cells are able to change the ways in which they adhere to one
another, they can extend processes and pull themselves along,
migrating to new locations, and they can change their own shapes.
In a tissue there may be a change in cell number, cell size or accretion of extracellular material. In these ways a tissue gains and
changes shape.
An early example of morphogenesis in embryonic development
occurs with the change from simple flat sheets of cells to the rolled
up tubes of the embryo and gastrointestinal tract (Figure 3.3). A
simple structure has become more complex. Chapter 13 covers this
in more detail.

Clinical relevance
Interruptions of signalling, proliferation, differentiation, migration, and so on, cause congenital abnormalities. Teratogens that
affect development during key periods may have significant effects.
For example, if the drug thalidomide is taken during early limb

development it can cause phocomelia (hands and feet attached to
abnormally shortened limbs). Other environmental factors and
genetic mutations can cause abnormal development. The embryo
is most sensitive during weeks 3–8.
Dysmorphogenesis is a term used for the abnormal development
of body structures. It may occur because of malformation or
deformation. If the processes required to normally form a structure fail to occur the result is a malformation. If the neural tube
fails to close, for example, the resulting neural tube defect is a
malformation. A deformation occurs if external mechanical forces
affect development. For example, damage to the amniotic sac can
cause amniotic bands that may wrap around developing limbs and
cause amputation of limbs or digits.

Introduction to development  Early development  15


4

Embryonic and foetal periods
Menstruation
(4–6 days)
Reparative
phase (4 days)
Secretory phase
(14 days)
Proliferative
phase (10–12 days)

Figure 4.1
The stages and timing of the menstrual cycle

Ovulation
(14 days before
menstruation starts)

Last menstruation
Fertilisation

Antepartum or perinatal period
Prenatal development

First trimester

Periods

Second trimester

Third trimester

Embryogenesis

Fetal development

Week no. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45
Month no.
1
2
3
4
5

6
7
8
9
10
50% survival chance

Birth
classification

Preterm

Figure 4.2
Clinical timings of gestation related to the embryonic and foetal periods

0

2

LMP

0

Embryo

Weeks of gestation
20

10
4

8

12

16

Childbirth average

Viability

20

Term

30
24

28

32

Postmature

40

Clinical timing

38

Embryological
timing

Foetus

Figure 4.3
The scale, in weeks, shows how gestation is dated clinically and embryologically.
LMP refers to the date of the ‘last menstrual period’, from which the clinical period of gestation is determined.
Embryologically speaking development of the new embryo begins with fertilisation. Clinically gestational timings
are around 2 weeks longer than an embryologists’ timing

Embryology at a Glance, First Edition. Samuel Webster and Rhiannon de Wreede.

16  © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

Birth


Time period: day 0 to birth
Embryonic period
The embryonic period is considered to be the period from fertilisation to the end of the eighth week. The period from fertilisation
to implantation of the blastocyst into the uterus (2 weeks) is sometimes called the period of the egg.
During the period of the egg the early zygote rapidly proliferates
to produce a ball of cells that makes its way along the uterine tube
towards the uterus. The complexity of the blastocyst increases as
it progresses towards the site of implantation.
During the embryonic period the major structures of the embryo
are formed, and by 8 weeks most organs and systems are established and functioning to some extent, but many are at an immature stage of development. At the end of the eighth week the
external features of the embryo are recognisable; the eyes, ears and
mouth are visible, the fingers and toes are formed, and limbs have

elbow and knee joints.

Foetal period
From the ninth week to birth the foetus matures during the foetal
period. The foetus grows rapidly in size, mass and complexity, and
its proportions change (for example, head to trunk, and limbs).
The foetus’ weight increases considerably in the latter stages of the
foetal period. Organs and systems continue in their functional
development, and some systems change considerably at birth (for
example, the respiratory and circulatory systems).
Birth in humans normally occurs between 37 and 42 weeks after
fertilisation.

Trimesters
The nine calendar month gestation period is split into 3-month
periods called trimesters. During the first trimester the embryonic
and early foetal periods occur. In the second trimester the uterus
becomes much larger as the foetus grows considerably, and symptoms of morning sickness tend to subside. A foetus in the third
trimester turns and the head drops into the pelvic cavity (engagement) in preparation for birth. Babies born prematurely during
the third trimester may survive, particularly with specialised intensive care treatment.

Clinical and embryological timings
Embryologists use timings from the date of fertilisation, and all
the timings in this book will relate to that time. Embryologists
studying the embryos of animals often have an advantage in being
able to fairly accurately note when fertilisation occurred. Clinically, the date of fertilisation is more difficult to determine.
A woman’s menstrual cycle will take around 28 days to complete, starting with the first day of the menstrual period (bleed)
and returning to the same point (Figure 4.1). Menstruation occurs
for 3–6 days, followed by the proliferative phase for 10–12 days.
Ovulation occurs around 14 days before the start of the next menstrual period. If the released ovum is fertilised menstruation will

not occur. Fertilisation must occur within 1 day of ovulation.
The event of the last menstrual period can be used to date the
period of gestation clinically, although the date on which fertilisation took place will be uncertain because of variability in the length
of the cycle between the start of menstruation and ovulation.
Clinically, gestational timings are around 2 weeks longer than
an embryologist’s timing (Figure 4.2). If the embryonic period is
complete at the end of week 8, a clinician would record this as the
end of week 10 (Figure 4.3).

Clinical relevance
If you are a medical, nursing or health sciences student then you
must be aware of the 2-week difference between embryologists’
and clinicans’ gestation timings.
A gestation period of 40 weeks is equal to 10 lunar months. A
period of 10 lunar months is, on average, 7 days longer than any
9 calendar months. Using the mother’s date of the start of her last
menstrual period you can quickly calculate an estimated date of
delivery by adding 9 calendar months and 7 days.
An awareness of the period of the egg, the embryonic period
and the trimesters helps understand the periods of susceptibility of
the embryo and the foetus. For example, after the period of the
egg and during the embryonic period the embryo is particularly
vulnerable to the effects of teratogens and environmental insults.
The respiratory system develops significantly during the third trimester, so linking the timing of a premature birth to the potential
requirements of the baby are important.

Embryonic and foetal periods  Early development  17


5

Mitosis
M
Nucleus
Chromosomes
(green)
G1

G2

Figure 5.2
Interphase
A single cell in interphase (i.e. not in mitosis)

Figure 5.1
S
The cell cycle
G1, S and G2 are parts of the cell cycle (we call them interphase in this chapter)
and M indicates mitosis. Note that a single chromosome in G1 is duplicated during
the DNA synthesis phase (S), and a chromosome made up of two, identical sister
chromatids is ready to enter mitosis in G2 phase

Figure 5.3
Parts of a
chromosome
during cell
division

Chromatid
Centromere

Chromosomes (green)
Centromere (red)
Nuclear membrane

specific sequence of DNA found nearly central on the chromosome.
This region links the chromosome to the spindles necessary for mitosis

Centrioles

a collection of microtubules in a 9-triplet arrangement, with the 2
centrioles at right angles to each other. They hold the microtubules
spindles as the chromosomes attach ready to divide

Microtubules
Prophase
Nuclear membrane
breaking up

Microtubules
Prometaphase

Metaphase

Anaphase

New nuclear
membrane forming
Chromosomes
become less condensed

Telophase

Cell splits in two

Figure 5.4
Stages of mitosis

Embryology at a Glance, First Edition. Samuel Webster and Rhiannon de Wreede.

18  © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.

Daughter cells


Time period: day 0 to adult
Cell division
Cell division normally occurs in eukaryotic organisms through the
process of mitosis, in which the maternal cell divides to form two
genetically identical daughter cells (Figure 5.1). This allows
growth, repair, replacement of lost cells and so on. A key process
during mitosis is the duplication of DNA to give two identical sets
of chromosomes, which are then pulled apart and new cells are
formed around each set. The new cells may be considered to be
clones of the maternal cell.

Mitosis
A cell dividing by mitosis passes through six phases.
• Interphase: the cell goes about its normal, daily business (Figure
5.2). This is also known as the cell cycle, and includes phases of

its own: G1 (gap 1), S (synthesis) and G2 (gap 2). DNA is duplicated (synthesised) during S phase.
• Prophase: DNA condenses to become chromosomes which are
visible under a microscope (Figure 5.3). Centrioles move to opposite ends of the cell and extend microtubules out (this is the mitotic
spindle). The centromeres at the centre of the chromosomes also
begin to extend fibres outwards (Figure 5.4).
• Prometaphase: the nuclear membrane disappears, microtubules
attach centrioles to centromeres and start pulling the chromosomes.

• Metaphase: chromosomes become aligned in the middle of
the cell.
• Anaphase: chromosome pairs split (centromeres are cut), and
one of each pair (sister chromatids) move to either end of the
cell.
• Telophase: sister chromatids reach opposite ends of the cell and
become less condensed and no longer visible; new membranes
form around the new nuclei for the daughter cells.
• Cytokinesis: an actin ring around the centre of the cell shrinks
and splits the cell in two.
• Interphase: the cell goes about its normal, daily business (including preparing for and doubling its DNA to form pairs of
chromosomes).

Clinical relevance
Errors in mitotic division, although rare, will be carried into
the daughter cells of that division, and onwards to new cells produced from them. Errors in early embryonic development could
have catastrophic consequences, as an error in one cell would
quickly become an error in a huge number of cells. Chromosomal
damage can give small or significant effects, such as trisomy
(an extra copy of a chromosome), or translocation or inversion
of a broken section. Trisomy 21, for example, results in Down
syndrome.

Mitosis  Early development  19


6

Meiosis

1

2

3

4

5

6

7

8

9

10

11

12

13

14

15

16

17

18

19

20

21

22

X

Y

Figure 6.1
Human karyotype
(23 pairs of chromosomes condensed in prophase).
A pair is formed by two identical sister chromatids,

two separate chromosomes with the same genes
but potentially different alleles (copies of those genes)

Sister
chromatids

Figure 6.2
A chromosome in the G1 phase
after mitosis (interphase)

Figure 6.3
A chromosome after S phase. The DNA has been
duplicated to produce two identical sister chromatids

Figure 6.4
A homologous pair of chromosomes (meiosis)

Red and green strands are pairs of (homologous) chromosomes
(a pair has one red and one green chromosome). The red strand
signifies the paternal DNA and the green strand the maternal
DNA within this cell
Homologous chromosomes begin to
swap sections of DNA (alleles)

Interphase

Prophase I

Prometaphase I

Homologous
chromosomes

Metaphase I

Anaphase I

Telophase I

Interphase II

Figure 6.5
Meiosis I is similar to mitosis, but at the end of meiosis I two cells have formed, each with one chromosome of a homologous pair.
They are haploid cells. Note the crossover of alleles between homologous pairs

Anaphase II
Telophase II
4 haploid cells
Metaphase II
Figure 6.6
In the two haploid cells division begins again. At the end of meiosis II four haploid cells have formed, each with 23 chromosomes
(not paired) and a mix of maternally and paternally derived alleles
Embryology at a Glance, First Edition. Samuel Webster and Rhiannon de Wreede.

20  © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.


Time period: day 0 to adult
Diversity
Cell division by mitosis gives no opportunity for change or diversity, which is ideal for processes like growth and repair. In humans,

sexual reproduction allows random mingling of maternal and
paternal DNA to produce a new, unique individual. This is able
to occur because of a different type of cell division called meiosis.
During meiosis a single cell divides twice to form four new cells.
These daughter cells have half the normal number of chromosomes (they are haploid cells). Meiosis is the method of producing
spermatozoa and oocytes. When an egg is fertilised by a sperm the
chromosomes will combine to form a cell with the normal number
of chromosomes.

Human chromosomes
There are 23 pairs of human chromosomes (Figure 6.1) in a normal,
diploid cell (from the Greek word diploos, meaning ‘double’). Each
chromosome is a length of DNA wrapped into an organised structure (Figure 6.2). Twenty-two of the pairs of chromosomes are
known as autosomes. The remaining pair are known as the sex
chromosomes, which hold genes linked to the individual’s sex.
When condensed the pairs of autosomes look like X’s (Figures 6.3
and 6.4), and the sex chromosomes look like X’s or Y’s (Figure 6.1).
The female sex chromosome pair appears as XX, the male as XY.

Meiosis I
A cell dividing by meiosis divides twice (meiosis I and meiosis II).
During meiosis I (Figure 6.5), a cell passes through phases very
similar to those of mitosis, but with some significant differences.
It begins with 23 pairs of chromosomes (46 chromosomes in total).
• Interphase: the cell goes about its normal, daily business (diploid).
• Prophase I: homologous chromosomes exchange DNA (homologous recombination); chromosomes condense and become visible;
centrioles move to opposite ends of the cell and extend microtubules out (mitotic spindle); centromeres extend fibres out from
chromosomes (diploid).
• Prometaphase I: the nuclear membrane disappears, microtubules
attach centrioles to centromeres and start pulling the chromosomes (diploid).

• Metaphase I: chromosomes are aligned in the middle of the cell
(diploid).
• Anaphase I: homologous chromosome pairs split, one of each
pair (each pair has two chromatids) moving to either end of the
cell (diploid).
• Telophase I: homologous chromosomes reach each end of the
cell; new membranes form around the new nuclei for the daughter
cells (diploid).
• Cytokinesis: an actin ring around the centre of the cell shrinks
and splits the cell in two (haploid).
After meiosis I each cell has 23 chromosomes, and each chromosome has two chromatids. It is therefore haploid.

Homologous recombination
The key event during meiosis I is the separation of homologous
chromosomes, rather than the separation of sister chromatids as
occurs during mitosis. But what are homologous chromosomes?
Sister chromatids (Figure 6.4) are identical copies of DNA that
are attached to one another by the centromere to form the

X-shaped chromosomes that we recognise. So, when sister chromatids are separated into two new cells by mitosis the new cells
will be genetically identical.
Homologous chromosomes (Figure 6.4) are the two chromosomes that make up the ‘pair’ of chromosomes that we talk about
in diploid cells. We say that human diploid cells contain 23 pairs
of chromosomes. They are homologous in that they are the same
chromosome but with subtle differences. One chromosome has
been inherited from the father and one from the mother.
Homologous chromosomes contain genes for the same biological features, but the genes may be slightly different. For example,
the genes for eye colour would be found on both homologous
chromosomes but one chromosome may hold the gene that
encodes for blue eyes and the other for green eyes. These are different alleles of the same gene.

During homologous recombination those genes are swapped
around randomly between the homologous chromosomes before
they are pulled into new cells. Therefore, each new cell could be
quite different with many, many genes randomly exchanged. In
this way the gametes (eggs, sperm) formed by meiosis become very
diverse.
The female sex chromosomes (XX) are homologous, but the
male sex chromosomes (XY) are not.

Meiosis II
Without replicating its DNA the cell moves from meiosis I to
meiosis II. Meiosis II is very similar to mitosis.
• Prophase II: chromatids condense and become visible; centrioles
move to opposite ends of the cell and extend microtubules out
(mitotic spindle); centromeres extend fibres out from chromosomes (haploid).
• Prometaphase II: the nuclear membrane disappears, microtubules attach centrioles to centromeres and start pulling the chromosomes (haploid).
• Metaphase II: chromosomes are aligned in the middle of the cell
(haploid).
• Anaphase II: chromosome pairs split (centromeres cut), one of
each pair (sister chromatids) moving to either end of the cell
(haploid).
• Telophase II: sister chromatids reach opposite ends of the cell;
new membranes form around the new nuclei for the daughter cells
(haploid).
• Cytokinesis: an actin ring around the centre of the cell shrinks
and splits the cell in two (haploid).
The end result is, generally speaking, 4 cells with 23 unpaired
chromosomes each (Figure 6.6). We will find out more about this
in the gamete chapters (see Chapter 7, spermatogenesis and
Chapter 8, oogenesis).

Clinical relevance
Karyotyping and comparing a patient’s chromosomes to the
expected normal chromosomal pattern is important in diagnosing
a number of chromosomal abnormalities, such as trisomy 21
(Down syndrome), XXY (Klinefelter syndrome) and trisomy 18
(Edwards syndrome).
The homologous recombination of prophase I is an important
mechanism of Mendelian inheritance. It is a key tenet of modern
genetics and underlies most clinical disorders with a genetic basis.
Meiosis  Early development  21


7

Spermatogenesis

Testicular
artery

Spermatogonia A
(pool of proliferating cells)

XY
Pampiniform
plexus

Vas deferens

Epididymis

Tunica
vaginalis

XY

Spermatogonia B
(diploid)

Testis

Primary spermatocyte
(diploid)

XY
Meiosis I

Figure 7.1
Anatomy of the testis and epididymis

Head

Mid
(connecting)
piece

Plasma membrane
Acrosome
Nucleus
Centriole

X

Secondary spermatocyte
(haploid)

Y
Meiosis II

X

X

Y

Y

Spermatids
(haploid)

Spermiogenesis

Mitochondria
Terminal disc

X

X

Y

Y

Spermatozoa
(haploid)

Axial filament
Tail

Figure 7.2
Spermatogenesis
Note that the cytoplasmic bridges between cells are not shown here
for simplicity. Cells linked together by these bridges pass through
spermatogenesis in synchronisation

End
piece

Figure 7.3
A mature human spermatozoon

Embryology at a Glance, First Edition. Samuel Webster and Rhiannon de Wreede.

22  © 2012 John Wiley & Sons, Ltd. Published 2012 by John Wiley & Sons, Ltd.


Time period: puberty to death
Meiosis continued
In the last chapter we talked about the importance of meiosis in
sexual reproduction and diversity, and saw how haploid cells are
formed. In males, meiosis occurs during spermatogenesis, in which

spermatogonia in the testes become spermatozoa.
The germ cells that will form the male gametes (spermatozoa)
are derived from germ cells that migrate from the yolk sac into the
site of early gonad formation (see Chapter 36).

Aims of spermatogenesis
Spermatogonia are diploid germ cells in the testes that maintain
their numbers by mitosis, thus maintaining spermatozoa numbers
through life. Spermatogonia contain both X and Y sex chromosomes. At a certain point a spermatogonium will stop its other
duties and begin meiosis. The cells that result will then pass
through more stages of maturation and development and will
become mature spermatozoa capable of travelling to and fertilising
an ovum.

Anatomy
The testis is made up of very long, tightly coiled tubes called the
seminiferous tubules that are surrounded by layers of connective
tissue, blood vessels and nerves (Figure 7.1). The seminiferous
tubules are linked to straight tubules and a network of tubes called
the rete testis which lead to the epididymis. The epididymis is
another collection of tubes on the posterior edge of the testis that
passes inferiorly and is continuous with the ductus deferens (also
known as the vas deferens). The ductus deferens carries mature
spermatozoa from the testis to the urethra.
Spermatogonia are found in the walls of the seminiferous
tubules, and as they progress through spermatogenesis they pass
towards the lumina of those tubules. Leydig cells within the testes
produce testosterone. Sertoli cells are also found in the seminiferous tubules, and produce a number of hormones.

Spermatocytogenesis

The spermatogonia that we begin the process with are called spermatogonia A cells (Figure 7.2). These are the stem cells that proliferate and replenish the root source of all spermatozoa. The cells
that are about to begin meiosis are called spermatogonia B cells,
and can be recognised partly because they are connected to one

another by cytoplasmic bridges. They continue to divide by mitosis
until they become primary spermatocytes. The cytoplasmic bridges
will maintain connections between a group of cells during spermatogenesis, synchronising the process and batch producing groups
of spermatozoa.
The primary spermatocytes enter meiosis I. Homologous recombination of chromosomes occurs in this stage. One primary spermatocyte becomes two secondary spermatocytes. These cells are
now haploid. Each secondary spermatocyte may contain an X or
a Y sex chromosome.
Secondary spermatocytes enter meiosis II and again divide,
forming spermatids. As the DNA was not replicated in meiosis II
these cells have half their original DNA. During fertilisation this
DNA will be combined with the DNA of the maternal ovum. This
is the end of the first stage of spermatogenesis, known as
spermatocytogenesis.

Spermiogenesis
During spermiogenesis the rounded spermatid cell changes shape,
becoming elongated and developing the familiar head and tail. The
cell loses cytoplasm, the nucleus is packed into the head, mitochondria become concentrated in the first part of the tail and an
acrosome forms around the tip of the head. The acrosome contains
enzymes that will help the sperm penetrate the outer layers of the
ovum during fertilisation.
At the end of spermiogenesis the spermatids have become spermatozoa (Figure 7.3).

Spermatozoa
Spermatogenesis takes around 64 days to produce spermatozoa
from germ cells in the above processes. The spermatozoa are then

passed in an inactive state to the epididymis, where they continue
to mature. During the next week they descend within the epididymis and become motile and ready to be passed into the ductus
deferens during ejaculation.

Clinical relevance
Abnormalities in spermatogenesis are common, and during fertility investigations the number and concentration of spermatozoa,
and the proportion of abnormal sperm, are counted in a semen
sample. A number of biological and environmental factors will
affect the sperm count and fertility, such as smoking, sexually
transmitted diseases, toxins, testicular overheating and radiation.

Spermatogenesis  Early development  23